• COMMENT

What Rosalind Franklin truly contributed to the discovery of DNA’s structure

Franklin was no victim in how the DNA double helix was solved. An overlooked letter and an unpublished news article, both written in 1953, reveal that she was an equal player.
By
  1. Matthew Cobb
    1. Matthew Cobb is professor of zoology at the University of Manchester, UK.

    You can also search for this author inPubMed Google Scholar

  2. Nathaniel Comfort
    1. Nathaniel Comfort is professor of history of medicine at Johns Hopkins University, Baltimore, Maryland, USA.

    You can also search for this author inPubMed Google Scholar

Black and white image of Rosalind Franklin resting on a post while out hiking in Norway

Chemist Rosalind Franklin independently grasped how DNA’s structure could specify proteins. Credit: Photo Researchers/Science History Images/Alamy

You have full access to this article via your institution.

James Watson and Francis Crick are two of the twentieth century’s most renowned scientists. The seminal paper from the pair at the University of Cambridge, UK, detailing the discovery of the DNA double helix, was published as part of a trio inNature 70 years ago this week13. They are also widely believed to have hit on the structure only after stealing data from Rosalind Franklin, a physical chemist working at King’s College London.

Lore has it that the decisive insight for the double helix came when Watson was shown an X-ray image of DNA taken by Franklin — without her permission or knowledge. Known as Photograph 51, this image is treated as the philosopher’s stone of molecular biology, the key to the ‘secret of life’ (not to mention a Nobel prize). In this telling, Franklin, who died of ovarian cancer in 1958 at just 37, is portrayed as a brilliant scientist, but one who was ultimately unable to decipher what her own data were telling her about DNA. She supposedly sat on the image for months without realizing its significance, only for Watson to understand it at a glance.

This version of events has entered into popular culture. It is the subject ofPhotograph 51,a play by Anna Ziegler that starred Nicole Kidman on the London stage in 2015. The image graces a British 50 pence coin that marked the centenary of Franklin’s birth, in 2020. The whole affair has provided fodder for scornful Twitter jokes (“What did Watson and Crick discover in 1953? Franklin’s data.”) and even amarvellous rap battle by seventh-grade students in Oakland, California.

But this is not what happened.

How Rosalind Franklin was let down by DNA’s dysfunctional team

One of us (N.C.) is writing a biography of Watson, the other (M.C.) is writing one of Crick. In 2022, we visited Franklin’s archive at Churchill College in Cambridge, UK, and went through her notes together, reconstructing the development of her ideas. We also found a hitherto unstudied draft news article from 1953, written in consultation with Franklin and meant forTime, a US magazine with international reach — as well as an overlooked letter from one of Franklin’s colleagues to Crick. Together, these documents suggest a different account of the discovery of the double helix. Franklin did not fail to grasp the structure of DNA. She was an equal contributor to solving it.

Getting Franklin’s story right is crucial, because she has become a role model for women going into science. She was up against not just the routine sexism of the day, but also more subtle forms embedded in science — some of which are still present today.

Franklin and DNA

In the early 1950s, the structure and function of DNA remained unclear. It had been found in every cell type investigated, and was known to consist of a phosphate backbone to which were attached four kinds of base — adenine, thymine, cytosine and guanine (A, T, C and G).

In 1944, the microbiologist Oswald Avery and his colleagues had shown that DNA (not protein) could transform benignStreptococcus pneumoniae bacteria into a virulent form4. But it remained far from clear that it was the genetic material in all organisms.

At King’s College London, biophysicists funded by the Medical Research Council (MRC), and led by John Randall, with Maurice Wilkins as his deputy (who would later share the Nobel prize with Watson and Crick in 1962), were using X-ray diffraction to study the structure of the molecule. In 1951, they were joined by Franklin, who had been using this technique to investigate the structure of coal at the Central State Laboratory of Chemical Services in Paris.

Photograph of Maurice Wilkins, James Watson and Francis Crick at the 1962 Nobel Prize ceremony

Maurice Wilkins (left), James Watson and Francis Crick at the ceremony for the 1962 Nobel Prize in Physiology or Medicine.Credit: King’s College London Archives: K/PP178/15/3/1

As is well known, Franklin and Wilkins clashed, in both personality and scientific approach. Although Franklin relished a good argument and was determined to make progress, Wilkins abhorred confrontation and was slower to act. To ease tensions, Randall divvied up the DNA work. In what Wilkins later called a bad bargain for himself, he agreed to turn over to Franklin the small supply of very pure DNA that he had obtained from the Swiss chemist Rudolf Signer. Wilkins was stuck with poorer quality stuff from the Austrian biochemist Erwin Chargaff, at Columbia University in New York City.

With the Signer DNA, Franklin was able to exploit a discovery that Wilkins had made earlier — DNA in solution could take two forms, what she called the crystalline or A form, and the paracrystalline or B form. Franklin found that she could convert A into B simply by raising the relative humidity in the specimen chamber; lowering it again restored the crystalline A form.

Franklin focused on the A form, Wilkins on the B form. To a physical chemist, the crystalline form seemed the obvious choice. When bombarded with X-rays in front of a photographic plate, it yielded sharp, detailed diffraction patterns. More detail meant more data, which meant a more accurate, albeit more difficult analysis. The B form, by contrast, yielded patterns that were blurrier and less detailed, but simpler to analyse. Initially, Franklin understood both A and B as helical. In notes for a seminar she gave in November 1951, she described them collectively: “big helix with several chains, phosphates on outside, phosphate–phosphate interhelical bonds, disrupted by water”5.

Unable to resolve the A-form structure, Franklin had decided by the middle of 1952 that it was not actually helical — she even teased Wilkins with a mock funeral notice for the crystalline DNA helix6. She was not alone in being thrown off by the A-form data: after the double-helix paper1 had been published, Crick wrote of Franklin’s precise but complex, data-rich A-form image, “I am glad I didn’t see it earlier, as it would have worried me considerably”7.

The double helix and the ‘wronged heroine’

As for the B form, she and everyone else at King’s recognized that it was some kind of helix. But to Franklin it was a distraction. At high humidity, water molecules crowded the atoms in DNA, producing a structure she described as “swollen”, “distended”, disordered. “Anyway,” she wrote in the notes for her 1951 seminar, under increased humidity, “the stuff ultimately dissolves, i.e. chains are separated from one another by water”5. She saw the B form as an artefact of being water-logged, a symptom of the loss of crystalline order — hence “paracrystalline”. This explains why, in late 1952 and early 1953, she rejected the argument that DNA was intrinsically helical.

From a chemist’s perspective, Franklin’s decision to focus on the crystalline A form was perfectly logical, as were the conclusions she drew from analysing it. But her focus on the drier A form ignored the very wet reality of the inside of a cell — which would mean that DNA took the more humid B form. Together with her insistence that the diffraction data be fully analysed before any modelling was attempted, it would hamper Franklin’s efforts for more than a year.

The meaning of Photograph 51

Even Franklin’s advocates often unwittingly perpetuate a caricatured view of her science — one that can be traced back to Watson’s reality-distorting 1968 bestseller,The Double Helix8. Watson’s version of the next, crucial stage in the story is often repeated to highlight how Franklin was deprived of due credit. Inadvertently, this undermines her.

According to Watson, in early 1953, he visited King’s and got into a row with Franklin. Wilkins, he wrote, rescued him from the confrontation and then showed him Photograph 51, a particularly clear image of the B form, taken 8 months earlier by Franklin and her graduate student Raymond Gosling. Franklin had put the photograph aside to concentrate on the A form. She was preparing to transfer to Birkbeck College, also in London, and had been instructed to leave her DNA work behind. Gosling was now being supervised by Wilkins, and he had given Wilkins the photograph. (He says he did so with Franklin’s knowledge9.) The image, Watson claimed inThe Double Helix, showed that a DNA helix “must exist” — only a helical structure could produce those marks8.

Because of Watson’s narrative, people have made a fetish of Photograph 51. It has become the emblem of both Franklin’s achievement and her mistreatment.

Black and white X-ray diffraction photograph of DNA from 1952

Franklin and Gosling’s X-ray diffraction image of B DNA, known as Photograph 51.Credit: King's College London Archives/Science Photo Library

But Watson’s narrative contains an absurd presumption. It implies that Franklin, the skilled chemist, could not understand her own data, whereas he, a crystallographic novice, apprehended it immediately. Moreover, everyone, even Watson, knew it was impossible to deduce any precise structure from a single photograph — other structures could have produced the same diffraction pattern. Without careful measurements — which Watson has insisted he did not make — all the image revealed was that the B form was probably some kind of helix, which no one doubted. Furthermore, various lines of evidence — includingThe Double Helix itself, read carefully — show that it played little, if any, part in Watson and Crick’s inching towards the correct structure between January and March 1953. In fact, it was other data from Franklin and Wilkins that proved crucial, and even then, what really happened was less malicious than is widely assumed.

Watson did get a jolt from seeing the photograph — because of when he saw it. Just days before, the Cambridge group had received a manuscript from the US chemist Linus Pauling, in which he’d claimed to have solved the DNA structure. Although Pauling had made some elementary errors, Lawrence Bragg, head of the Cavendish Laboratory, who had a long-standing rivalry with Pauling, had encouraged Watson and Crick to resume their model building. Watson had dropped in at King’s to show off Pauling’s blunder, and Wilkins had shown him the photograph. Fashioning that moment into the climax ofThe Double Helix was a literary device: a classic eureka moment, easy for lay readers to understand.

From 1951, Wilkins had kept Watson and Crick abreast of his work on the B form, in particular his belief that the structure contained one or more helices, repeated every 34 angstroms, and he might have said that within each repeat there were probably 10 elements. Shortly after Watson saw Photograph 51, Crick’s supervisor, Max Perutz, handed them an informal report of the activity of the King’s MRC unit, which he had been given as part of an official visit to the unit in December 1952. This included a page from Franklin, describing her work. In a 1969 letter toScience, although Perutz said that he regretted sharing the report without first consulting the King’s group, it was not confidential10. Indeed, a letter we have discovered from a King’s researcher, Pauline Cowan, written to Crick in January 1953, invites Crick to a talk by Franklin and Gosling, who, Cowan continues, “say that it is mostly for a non-crystallographic audience + that Perutz already knows more about it than they are likely to get across so you may not think it worthwhile coming”. Thus, Franklin seems to have assumed that Perutz would share his knowledge with Crick as part of the usual informal scientific exchange11.

In her contribution to the MRC report, Franklin had confirmed the 34 Å result for the B form. She also reported that the unit cell (the repeating unit of the crystal) of DNA was huge; it contained a larger number of atoms than any other unit cell in any other known molecular structure. Franklin also added some key crystallographic data for the A form, indicating that it had a ‘C2’ symmetry, which in turn implied that the molecule had an even number of sugar-phosphate strands running in opposite directions.

Notes by Crick for a lecture on the history of the double helix, given to historians of science at the University of Oxford in May 1961, together with formal and informal remarks made throughout his life, reveal that, unlike Photograph 51, this report was truly significant for confirming the structure that Watson and Crick eventually obtained.

In the end, however, neither Photograph 51 nor the MRC report ‘gave’ Watson and Crick the double helix. What did was six weeks of what they later described as “trial and error” — making chemical calculations and fiddling about with cardboard models. (Watson made this plain inThe Double Helix; Crick did so in a series of interviews with the historian Robert Olby in the late 1960s and early 1970s.)

Franklin’s data and Watson and Crick’s many conversations with Wilkins had provided what seem like key pieces of information — the phosphate groups were on the outside of the molecule; there was a repeat every 34 Å; perhaps there were ten bases per repeat and an even number of strands running in opposite directions (the implication of the C2 symmetry). Yet, according to their own accounts, the pair ignored every one of these facts at one point or another during those six weeks. Once they had hit on a conceptual model of the structure, the MRC report provided a valuable check on their assumptions.

So it was not a case of them stealing the King’s group’s data and then, voila, those data gave them the structure of DNA. Instead, they solved the structure through their own iterative approach and then used the King’s data — without permission — to confirm it.

What Franklin really did

Franklin contributed several key insights to the discovery of the double helix. She clearly differentiated the A and B forms, solving a problem that had confused previous researchers. (X-ray diffraction experiments in the 1930s had inadvertently used a mixture of the A and B forms of DNA, yielding muddy patterns that were impossible to fully resolve.) Her measurements told her that the DNA unit cell was enormous; she also determined the C2 symmetry exhibited by that unit cell12.

The C2 symmetry was one of 230 types of crystallographic 3D ‘space groups’ that had been established by the end of the nineteenth century. Franklin failed to appreciate its significance not because she was obtuse, but because she was unfamiliar with it. According to her colleague Aaron Klug, Franklin later said that she “could have kicked herself” for not realizing the structural implications13. Crick did realize the implications because he happened to have studied C2 symmetry intensely. But even he did not use Franklin’s determination of this symmetry when building the model; rather, it provided a powerful corroboration when their model was complete.

Black and white image of James Watson and Francis Crick with their model of part of a DNA molecule, 1953

James Watson (left) and Francis Crick modelled the structure of the DNA double helix.Credit: A. Barrington Brown, Gonville & Caius College/Science Photo Library

Enjoying our latest content?
Login or create an account to continue

  • Access the most recent journalism from Nature's award-winning team
  • Explore the latest features & opinion covering groundbreaking research

or

Nature616, 657-660 (2023)

doi: https://doi.org/10.1038/d41586-023-01313-5

References

  1. Watson, J. D. & Crick, F. H. C.Nature171, 737–738 (1953).

    Article PubMed  Google Scholar 

  2. Wilkins, M. H. F., Stokes, A. R. & Wilson, H. R.Nature171, 738–740 (1953).

    Article PubMed  Google Scholar 

  3. Franklin, R. E. & Gosling, R. G.Nature171, 740–741 (1953).

    Article PubMed  Google Scholar 

  4. Avery, O. T., MacLeod, C. M. & McCarty, M.J. Exp. Med.79, 137–158 (1944).

    Article PubMed  Google Scholar 

  5. Franklin, R. Notes for Colloquium on Molecular Structure, November 1951. Franklin Papers FRKN 3/2, Churchill College Cambridge, UK.

  6. Franklin, R. & Gosling, R. Joke death notice for the DNA helix, 1952. Wilkins Papers K/PP178/2/26, King’s College London.

  7. Crick, F. Letter to M. Wilkins, 5 June 1953. Brenner Papers SB/1/1/177, Cold Spring Harbor Laboratory Archives, USA.

  8. Watson, J. D.The Double Helix Ch. 23 (Atheneum, 1968).

    Google Scholar 

  9. Nature496, 270 (2013).

    Article PubMed  Google Scholar 

  10. Perutz, M. F., Randall, J. T., Thomson, L., Wilkins, M. H. F. & Watson, J. D.Science164, 1537–1539 (1969).

    Article PubMed  Google Scholar 

  11. Cowan, P. Letter to F. Crick, January 1953. Crick Papers Box 2, Folder 11, University of California San Diego, USA.

  12. Randall, J. Notes on current research prepared for the visit of the Biophysics Research Committee, 15 December 1952. Wilkins Papers K/PP178/2/22, King’s College London.

  13. Klug, A.J. Mol. Biol.335, 3–26 (2004).

    Article PubMed  Google Scholar 

  14. Maddox, B.Rosalind Franklin: The Dark Lady of DNA (HarperCollins, 2002).

    Google Scholar 

  15. Gulland, J. M.Cold Spring Harbor Symp. Quant. Biol.12, 95–103 (1947).

    Article  Google Scholar 

  16. Watson, J. D.Genes, Girls and Gamow Ch. 4 (Oxford Univ. Press, 2001).

    Google Scholar 

  17. Crick, F. H. C. & Watson, J. D.Proc. R. Soc. Lond. A223, 80–96 (1954).

    Article  Google Scholar 

  18. Bruce, J. Draft article on discovery of double helix, May 1953. Franklin Papers FRKN 6/4, Churchill College Cambridge, UK.

  19. Fourcade, B. Letter to J. Watson, 30 May 1953. Watson Papers JDW/2/2/614, Cold Spring Harbor Laboratory Archives, USA.

  20. de Chadarevian, S.Isis94, 90–105 (2003).

    Article PubMed  Google Scholar 

  21. Anon.Notes Rec. R. Soc. London11, 1–5 (1954).

    Article  Google Scholar 

  22. Judson, H. F.The Eighth Day of Creation: Makers of the Revolution in Biology (Cold Spring Harbor Laboratory Press, 1996).

    Google Scholar 

  23. Maddox, B.Nature421, 407–408 (2003).

    Article PubMed  Google Scholar 

Download references

Reprints and permissions

Competing Interests

The authors declare no competing interests.

Related Articles

Subjects

Latest on:

Nature Careers

Jobs

Related Articles

Subjects

Sign up to Nature Briefing

An essential round-up of science news, opinion and analysis, delivered to your inbox every weekday.

Nature Briefing

Sign up for theNature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox.Sign up for Nature Briefing